Endogenous and exogenous hydrogen sulfide promotes resolution of colitis in rats
Open accessAbstract
Background & aims Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator of mucosal defense with antiinflammatory effects that promote ulcer healing. The effects of H(2)S during the pathogenesis of colitis have not been established. We analyzed the contribution of H(2)S to inflammation and ulceration of the colon in a rat model of colitis.Methods Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid. The ability of the colon to synthesize H(2)S was studied over the course of the resolution of the colitis. Expression of 2 enzymes involved in the synthesis of H(2)S and the effects of inhibitors of these enzymes were examined. We also examined the effects of H(2)S donors on the resolution of colitis.Results The capacity for the colon to produce H(2)S increased markedly over the first days after induction of colitis and then declined toward control levels as the colitis was resolved. Inhibition of colonic H(2)S synthesis markedly exacerbated the colitis, resulting in significant mortality. Inhibition of H(2)S synthesis in healthy rats resulted in inflammation and mucosal injury in the small intestine and colon along with down-regulation of cyclooxygenase-2 messenger RNA expression and prostaglandin synthesis. Intracolonic administration of H(2)S donors significantly reduced the severity of colitis and reduced colonic expression of messenger RNA for the proinflammatory cytokine tumor necrosis factor alpha.Conclusions In rats, H(2)S modulates physiological inflammation and contributes to the resolution of colitis.
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The doses of PAG and CHH used have been shown to significantly inhibit CSE and CBS activities in rats.
“These doses of PAG and CHH have been shown to significantly inhibit CSE and CBS activities in rats [34], [35].”
From Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis (2014) · cites this paper as [35]
The Effects of Inhibitors section (page unavailable) identifies PAG as a CSE inhibitor and CHH as a CBS inhibitor, and reports testing them on rat colonic tissue. But the Figure 3 caption (page unavailable) says that, at 3 mmol/L, only CHH significantly reduced H₂S synthesis in healthy tissue; it does not show significant inhibition by PAG at that concentration. The reported endpoint was H₂S synthesis in tissue, not a direct measurement of both enzyme activities after dosing rats. (LLM, conf=0.86)
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“Suppression of endogenous H2S synthesis has been shown to impair gastric and colonic mucosal defence, and to impair healing of ulcers [26,27,34,35].”
BackgroundSelf-citation
- Authors
- Wallace, J. L., Vong, L., McKnight, W., Dicay, M., & Martin, G. R.
- Affiliations
- University of Calgary (CA)
- Corresponding author
- Wallace, John L.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 137
- Issue
- 2
- Pages
- 569-578.e1
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2032861502
- Cited by
- 308
- References
- 49
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 24 · 2023: 17 · 2022: 18 · 2021: 24 · 2020: 12 · 2019: 18 · 2018: 19 · 2017: 30 · 2016: 20 · 2015: 18 · 2014: 19 · 2013: 24 · 2012: 14
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Association of Gastroenterology
- AstraZeneca Canada
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Surgery › Hydrogen's biological and therapeutic effects
- Keywords
- hydrogen sulfide, colitis, inflammation resolution, trinitrobenzene sulfonic acid, cyclooxygenase-2, prostaglandins, TNF-α, H2S donors, colonic ulceration, mucosal injury
- MeSH terms
- Analysis of Variance, Animals, Biopsy, Needle, Colitis, Disease Models, Animal, Glyburide, Hydrogen Sulfide, Immunohistochemistry, Male, Probability, Random Allocation, Sensitivity and Specificity, Trinitrobenzenesulfonic Acid, Tumor Necrosis Factor-alpha, Biomarkers, Survival Rate, Treatment Outcome, Rats, Wistar, Statistics, Nonparametric, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, Rats, Cyclooxygenase 1, Cyclooxygenase 2
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